In U.S. Pat. Nos. 4,950,224, 5,152,743, 5,151,082, 5,735,809 and 5,980,478 there are disclosed methods and apparatus for carrying out in-vivo plasmapheresis for separating plasma from other blood components within the body and blood vessels of the patient. The apparatus uses pumping means to create a trans-membrane pressure (TMP) and motivate the flow of fluid from within the in-vivo system, whereby blood plasma is pumped from the patient to a treatment means such as a dialyzer apparatus in which toxic metabolic waste in the plasma is removed. After the plasma is treated for removal of waste products, excess fluids, toxins, and/or other deleterious plasma proteins, the treated plasma is returned and reintroduced to the patients"" blood stream. Such methods are referred to as plasma dialysis, ultrafiltration or blood purification. The methods and apparatus described in the aforesaid patents are incorporated herein by reference.
These methods of toxin removal from blood as taught by the above patents are unique and substantially superior from conventional means of hemodialysis as presently practiced for both acute and chronic kidney failure, primarily because removal of whole a blood from the patient""s vasculature is eliminated from the procedure using plasma, or portions of the plasma instead. In conventional hemodialysis procedures hollow fiber membranes are used in the ex-vivo dialysis and hemofilter cartridges for blood purification. The blood is routed from the body through the center lumen of the hollow fibers in the cartridges and dialysate fluid is routed over the outside walls of the fibers within the cartridge cavity in counter-flow direction to blood flow. Thus, toxin diffusion and ultrafiltration are from inside the fiber lumen to a compartment outside the fiber walls where the ultrafiltrate and toxin-saturated dialysate are collected for further processing and/or disposal.
Conventional hollow fiber membranes commercially used for present hemodialysis, hemo-ultrafiltration, and dialyzer cartridges fabricated from proprietary and non-proprietary polymer compositions generally utilize two types of morphologies: symmetrical and asymmetrical. In a symmetrical composition, the basic morphology or cellular structure and porosity of the fiber wall is uniform from the inner lumen to the outside surface. In asymmetrical compositions, both morphology and pore structures vary from the inner lumen to the outer surface to meet the high pressure requirements of the filter cartridges in which the TMP inside the fiber lumen is high (100-300 mmHg) while the blood flow itself in the fibers is near stagnant (2-300 ml/min/7,000 fibers=0.042 ml/fiber). These commercial membranes generally also have poor structural strength, acceptable in an encapsulated device external to the body but which would not be acceptable for an in-vivo placement for safety reasons. Such conventional fiber membranes are not suitable for the demanding environment of the in-vivo, high blood flow (vena cava=2.5 1/min), low TMP (xe2x89xa650 mmHg), and unencapsulated environment of plasma extraction devices described by the aforesaid patent applications.
The present invention is directed to specialized hollow fiber membranes having the function of separation of plasma or a portion of the plasma from blood and having the unique morphology, performance properties and materials biocompatible characteristics necessary for effective and optimal utilization for in-vivo vascular implantation as the operating element in catheter-based devices as described in the aforesaid patents and other such similar devices for the separation and extraction of plasma and plasma components from the blood. The ultrafiltrate (exudate) may be transported ex-vivo via a catheter lumen where it is discarded, or treated by cascade filtration means, dialysis (solute diffusion) means, or other methods known to the art, and returned to the patient via a separate lumen in the catheter.
The hollow fiber membrane of the invention is tubular in shape and generally circular in cross-section, having a coaxial inner lumen along the length of the fiber in its center. The wall volume of the fibers is asymmetrical with a variable morphology from the outer diameter to that of the inner diameter, having a higher mass density at the outer wall and a lower mass density at the inner wall. The fibers are designed to facilitate ultrafiltration with the permeate outside the fibers and the exudate inside the fibers. The inner lumen of all fibers in a fiber extraction assembly are in direct fluid communication with the access lumen of the catheter which provides means for transporting the exudate ex-vivo.